We recently have found that obese patients rapidly losing weight develop cholesterol gallstones frequently (26% incidence) and rapidly (in less than 4 months). The development of gallstones is accompanied by increases in biliary cholesterol saturation and glycoproteins. Ursodeoxycholic acid (UDCA, 1200 mg/d) reduces saturation, blocks increases in glycoprotein, and prevents gallstones. Aspirin (1300 mg/d) reduces glycoprotein and blocks the rise in saturation but does not prevent gallstones. the aims of the proposed studies are to study in obese patients losing weight: 1) the incidence of gallstones 2) the natural history of the gallstones that form 3) the efficacy of ursodeoxycholic acid in gallstone dissolution 4) the efficacy and mechanism of action of UDCA or ibuprofen (1600 mg/d) in preventing gallstones 4) the pathogenesis of the gallstones 5) the genetic predisposition to gallstones. 142 obese patients undergoing weight loss will be followed prospectively by ultrasonography for the development of gallstones. 25 patients who develop gallstones will be randomized to receive either UDCA or placebo and treated for up to 12 mo. 70 additional patients beginning weight loss will be randomized to receive UDCA, ibuprofen or placebo for 12 weeks. Prior to beginning weight loss and after 4 and 12 weeks, they will undergo ultrasonography, determination of gallbladder emptying, and biliary duodenal drainage to collect bile. Bile will be analyzed for factors which may be pathogenetically important to gallstones-- cholesterol saturation, nucleation of cholesterol, glycoproteins, proteins, vesicular cholesterol, and calcium saturation. First degree relatives of patients and spouses of first degree relatives will be examined ultrasonographically for the presence of gallstones. The frequency of gallstones among relatives and spouse controls will be compared between patients who form and do not form gallstones.